Mucosal damage in Gastro Intestinal (GI) system happens due to stress and is more common in upper part of GI tract in patients admitted to Intensive Care Unit (ICU). This kind of injuries occurs in critically ill patients. Stress ulcer prophylaxis is necessary and increases the gastric (Power of Hydrogen) pH (more than 4) especially in stress exposure time. In this paper we provide an overview of stress ulcer and currently used preventive approaches for this complication in critically ill patients in ICU. Recent promotion in ICU care and increase in scientific knowledge about Stress-Related Mucosal Disease (SRMD) risk factors help us to reduce the number of patients develop stress ulcer. Prophylaxis can prevent significant bleeding and mortality.